publications

2025

1. Resting-State Functional near-Infrared Spectroscopy in Neurodegenerative Diseases – A Systematic Review

   Franziska Albrecht, Alexander Kvist, and Erika Franzén

   NeuroImage: Clinical, Jan 2025

   Abs DOI

   Objective To systematically review and summarize alterations found in resting-state activity as measured via functional near-infrared spectroscopy (fNIRS) in neurodegenerative diseases. Background fNIRS is a novel and emerging neuroimaging method suitable for a variety of study designs. Resting-state is the measure of brain activity in the absence of a task, which has been investigated for yielding information about neurodegenerative diseases, mainly using magnetic resonance imaging. We aimed to systematically review the usage of resting-state fNIRS (rsfNIRS) in neurodegenerative diseases. Inclusion criteria Studies investigating people diagnosed with a neurodegenerative disease and resting-state activity obtained with fNIRS using at least two channels. Methods We searched three databases for publications. After the screening, 16 studies were included in the systematic review. The quality of the studies was assessed, and data were extracted. Data were qualitatively synthesized and in the case of at least 10 similar studies, a meta-analysis was planned. Results Most studies investigated Mild cognitive impairment (50%), followed by Alzheimer’s disease (25%). Other neurodegenerative diseases encompassed Parkinson’s disease, Multiple sclerosis, and Amyotrophic lateral sclerosis. All studies reported oxygenated hemoglobin. Still, studies were heterogeneous in terms of study design, measurement duration, fNIRS device, montage, pre-processing, and analyses. A meta-analysis was not considered possible due to this heterogeneity. Conclusion rsfNIRS shows promise in neurodegenerative disease, as most studies have observed resting-state alterations when compared to healthy controls. However, inconsistencies across studies limit data comparison and meta-analysis. Hence, we strongly advocate the application of fNIRS reporting guidelines and the establishment of rsfNIRS-specific guidelines. This will ensure reliable and comparable results in future research.

2. AS-RTS - Comparison between Auditory Stroop with Pre-Defined Intervals and Auditory Stroop with Response Triggered Stimuli

   Alexander Kvist, and Andreas Wallin

   Jan 2025

   Abs DOI

   Comparison and validation between two versions of an Auditory Stroop test: Auditory Stroop standard (AS-S) and Auditory Stroop with Response Triggered Stimuli (AS-RTS). The auditory Stroop test (1) used in this study is a cognitive task which consists of two stimulus words "high" and "low" (in Swedish) delivered via headphones in a congruent or incongruent pitch level. The participant is asked to respond to the pitch of the stimulus, and not the word itself. Response time and accuracy is then calculated. The test is performed both while sitting (single task) and while walking (dual task), which allows for calculating dual-task interference on the motor or cognitive task. In the Auditory Stroop standard (AS-S), stimuli are delivered with a set inter-stimulus interval of 2.0-2.5 seconds, in a pre-determined randomized order. A complete description of the AS-S is published elsewhere (2). The design of the standard version (AS-S) can allow for a pause before the next stimuli, if the participant responds quickly to a stimulus. In the Auditory Stroop with Response Triggered Stimuli (AS-RTS), a new stimuli is presented as soon as the participant answers. This might allow for a more continuous cognitive load. To validate if the newly developed version (AS-RTS) is comparable in regards to the outcome measures accuracy and response time as the standard version (AS-S), agreement between the test outcomes with be evaluated. Furthermore, the study will explore the impact of the new version of the test on motor and cognitive dual-task performance in people with MS. This study is performed within an ongoing data collection in a study investigating a balance intervention in people with multiple sclerosis (MS): Motor-cognitive Performance in People With Multiple Sclerosis (HiBalance-MS), https://clinicaltrials.gov/study/NCT06312046 (1) Morgan, A. L., & Brandt, J. F. (1989). An auditory Stroop effect for pitch, loudness, and time. Brain and language, 36(4), 592-603. (2) Wallin, A., Franzén, E., Bezuidenhout, L., Ekman, U., Piehl, F., & Johansson, S. (2022). Cognitive-motor interference in people with mild to moderate multiple sclerosis, in comparison with healthy controls. Mult Scler Relat Disord, 67, 104181. doi:10.1016/j.msard.2022.104181

2024

1. Validation of fNIRS Measurement of Executive Demand during Walking with and without Dual-Task in Younger and Older Adults and People with Parkinson’s Disease

   Alexander Kvist, Lucian Bezuidenhout, Hanna Johansson, and 3 more authors

   NeuroImage: Clinical, Jan 2024

   Abs DOI

   Background Walking with a concurrent cognitive task (dual-task walking) can pose a challenge to some populations due to aging or neurodegenerative disease. These tasks require cognitive resources involving the prefrontal cortex and can be studied using functional near-infrared spectroscopy (fNIRS). An important step in understanding fNIRS measures during such walking tasks is validating that measures reflect the demands of the tasks and not confounding sources or movement artifacts. Aim This study aimed to investigate the validity of fNIRS measures of prefrontal cortex activity as an indicator of executive demand during usual walking (single-task) and dual-task walking against clinical and objective measures of motor behavior in young adults, older adults, and people with Parkinson’s disease (PD), by evaluating several validation hypotheses. Methods In total, 133 participants were recruited from younger adults (18–50 years, n = 42), older adults (≥60 years, n = 49) and people with PD (≥60 years, n = 42). Activity in the prefrontal cortex during walking with and without an auditory Stroop task was measured with fNIRS. A combined hemoglobin measure (correlation-based signal improvement, CBSI) was calculated for use in a region of interest analysis in the dorsolateral prefrontal cortex (dlPFC). Pre-registered hypotheses regarding convergent validity, discriminant validity and known group validity were tested. An exploratory analysis of different hemoglobin measures was also performed. Results Increases in dlPFC activity were found from single- to dual-task walking in the younger adults group and from rest to single-task walking in the older adults and PD groups. In line with hypotheses, a positive relationship was found between between dlPFC activity during dual-task walking and dual-task cost in the younger adults group, as well as a positive relationship to step time variability during single-task walking and a negative relationship to walking speed during single-task walking in the PD group. However, several clinical and gait measures lacked a relationship with dlPFC activity. Conclusion The fNIRS results point towards the CBSI measure of dlPFC activity being a valid measure of executive demand during both single and dual-task walking. Some relationships between clinical and gait measures and brain activity during walking need further investigation.

2. Validation of Algorithms for Calculating Spatiotemporal Gait Parameters during Continuous Turning Using Lumbar and Foot Mounted Inertial Measurement Units

   Alexander Kvist, Fredrik Tinmark, Lucian Bezuidenhout, and 3 more authors

   Journal of Biomechanics, Jan 2024

   Abs DOI

   Spatiotemporal gait parameters such as step time and walking speed can be used to quantify gait performance and determine physical function. Inertial measurement units (IMUs) allow for the measurement of spatiotemporal gait parameters in unconstrained environments but must be validated against a gold standard. While many IMU systems and algorithms have been validated during treadmill walking and overground walking in a straight line, fewer studies have validated algorithms during more complex walking conditions such as continuous turning in different directions. This study explored the concurrent validity in a population of healthy adults (range 26–52 years) of three different algorithms using lumbar and foot mounted IMUs to calculate spatiotemporal gait parameters: two methods utilizing an inverted pendulum model, and one method based on strapdown integration. IMU data was compared to a Vicon twelve-camera optoelectronic system, using data collected from 9 participants performing straight walking and continuous walking trials at different speeds, resulting in 162 walking trials in total. Intraclass correlation coefficients (ICCA,1) for absolute agreement were calculated between the algorithm outputs and Vicon output. Temporal parameters were comparable in all methods and ranged from moderate to excellent, except double support time which was poor. Strapdown integration performed better for estimating spatial parameters than pendulum models during straight walking, but worse during turning. Selecting the most appropriate model should take into consideration both speed and walking condition.

3. The fNIRS Reproducibility Study Hub (FRESH): Exploring Variability and Enhancing Transparency in fNIRS Neuroimaging Research

   Meryem Ayşe Yücel, Robert Luke, Rickson C. Mesquita, and 106 more authors

   Sep 2024

   Abs DOI

   In neuroimaging research, efforts to enhance replication and reproducibility have increased the focus on improving transparency, particularly in the complex data analysis processes. We conducted a multi-lab collaborative study involving 38 international teams that analyzed two functional Near-Infrared Spectroscopy (fNIRS) datasets. These teams tested seven group-level and forty individual-level hypotheses, and they submitted detailed reports on their analysis pipelines and testing outcomes. The results showed significant variability in hypothesis testing outcomes due to differences in analytical approaches. There was greater consensus in group-level analyses compared to individual-level analyses. Factors such as the pruning method, hemodynamic response function model and estimation, and statistical analysis space partly account for the variability in hypothesis testing outcomes. Additionally, we have found higher similarity in hypothesis testing outcomes across the researchers who reported higher confidence in their analysis skills. This study underscores the importance of complying with best practices in fNIRS analysis methodologies and the need for standardized analysis protocols to improve reliability and credibility.

2023

1. Using Functional Near-Infrared Spectroscopy to Measure Prefrontal Cortex Activity during Dual-Task Walking and Navigated Walking: A Feasibility Study

   Alexander Kvist, Lucian Bezuidenhout, Hanna Johansson, and 4 more authors

   Brain and Behavior, Sep 2023

   Abs DOI

   Introduction While functional near-infrared spectroscopy (fNIRS) can provide insight into motor-cognitive deficits during ecologically valid gait conditions, the feasibility of using fNIRS during complex walking remains unknown. We tested the process and scientific feasibility of using an fNIRS device to measure cortical activity during complex walking tasks consisting of straight walking and navigated walking under single and dual-task (DT) conditions. Methods Nineteen healthy people from 18 to 64 years (mean age: 45.7 years) participated in this study which consisted of three complex walking protocols: (i) straight walking, DT walking (walking while performing an auditory Stroop task) and single-task auditory Stroop, (ii) straight and navigated walking, and (iii) navigated walking and navigated DT walking. A rest condition (standing still) was also included in each protocol. Process feasibility outcomes included evaluation of the test procedures and participant experience during and after each protocol. Scientific feasibility outcomes included signal quality measures, and the ability to measure changes in concentration of deoxygenated and oxygenated hemoglobin in the prefrontal cortex. Results All participants were able to complete the three protocols with most agreeing that the equipment was comfortable (57.9%) and that the testing duration was adequate (73.7%). Most participants did not feel tired (94.7%) with some experiencing pain (42.1%) during the protocols. The signal qualities were high for each protocol. Compared to the rest condition, there was an increase in oxygenated hemoglobin in the prefrontal cortex when performing dual-task walking and navigation. Conclusion We showed that our experimental setup was feasible for assessing activity in the prefrontal cortex with fNIRS during complex walking. The experimental setup was deemed acceptable and practicable. Signal quality was good during complex walking conditions and findings suggest that the different tasks elicit a differential brain activity, supporting scientific feasibility.

2018

1. Identifying Pathogenic Amino Acid Substitutions in Human Proteins Using Deep Learning

   Alexander Kvist

   KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH) / KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Sep 2018

   Abs

   Many diseases of genetic origin originate from non-synonymous single nucleotide polymorphisms (nsSNPs). These cause changes in the final protein product encoded by a gene. Through large scale sequencing and population studies, there is growing availability of information of which variations are tolerated and which are not. Variant effect predictors use a wide range of information about such variations to predict their effect, often focusing on evolutionary information. Here, a novel amino acid substitution variant effect predictor is developed. The predictor is a deep convolutional neural network incorporating evolutionary information, sequence information, as well as structural information, to predict both the pathogenicity as well as the severity of amino acid substitutions. The model achieves state-of-the-art performance on benchmark datasets.